Co-infections by double-stranded DNA viruses after ex vivo T cell-depleted, CD34(+) selected hematopoietic cell transplantation Journal Article

Authors: Huang, Y. T.; Kim, S. J.; Lee, Y. J.; Burack, D.; Nichols, P.; Maloy, M.; Perales, M. A.; Giralt, S. A.; Jakubowski, A. A.; Papanicolaou, G. A.
Article Title: Co-infections by double-stranded DNA viruses after ex vivo T cell-depleted, CD34(+) selected hematopoietic cell transplantation
Abstract: Recipients of ex vivo T cell–depleted (TCD) hematopoietic cell transplantation (HCT) are at risk of infection by double-stranded (ds) DNA viruses. We report rates of dsDNA viremia, end-organ disease (EOD), infection-related mortality, and overall survival (OS) in a contemporary cohort of adult TCD HCT recipients routinely monitored for cytomegalovirus (CMV), adenovirus (ADV), human herpesvirus 6 (HHV6), and Epstein-Barr virus (EBV). Healthcare utilization in the first 6 months post-HCT was compared between patients with dsDNA viremia versus no viremia. This was an observational study of adult patients with acute leukemia and myelodysplastic syndrome who received CD34+ selected, peripheral blood HCT at Memorial Sloan Kettering Cancer Center from March 2012 through December 2014. Patients were prospectively monitored by quantitative PCR assays for CMV, ADV, HHV6, and EBV in whole blood or plasma. The cumulative incidence of viremia(s) at day +180, EOD at 1 year, and OS at 1 year were estimated by the Kaplan-Meier method and compared by the log-rank test among patient with and without viremia/EOD. Standardized incidence ratios were used to compare overall length of hospital stay (LOS), number of readmissions after HCT, and length of readmissions through day +180. Of 156 patients, 96 (62%) were CMV recipient seropositive. Forty-two patients received grafts from matched related (27%), 86 from matched unrelated (55%), and 28 from mismatched (18%) donors. Overall, 132 patients (85%) had ≥1 viremia and 52 (33%) ≥2 viremias by day +180. The cumulative incidences for CMV, HHV6, ADV, and EBV viremia were 44%, 61%, 7%, and 16%, respectively, with median times of onset 28 days (interquartile range [IQR], 25 to 33), 33 days (IQR, 25 to 47), 60 days (IQR, 19 to 84), and 79 days (IQR, 54 to 106) post-HCT, respectively. Twenty-eight patients (18%) developed EOD by dsDNA viruses at 1 year post-HCT. Treatment for CMV accounted for 91% total antiviral treatment-days. Compared with patients with no viremia, patients with CMV viremia, HHV6 viremia, or ≥2 viremias experienced longer LOS (P <.001) and a higher number of readmissions (P <.001) by day +180. OS rate at 1 year was 79% and was similar between patients with or without dsDNA viremias. EOD was associated with lower 1-year OS rates (63.4%) versus without EOD (81.1%) (P =.02). Of 33 patients who died, 10 died due to infection, and 7 of these infection-related deaths were due to dsDNA viruses. Viremia by dsDNA viruses occurred in 85% of TCD HCT recipients by day +100 and 33% of patients experienced ≥2 viremias by day +180. CMV accounted for most antiviral use. CMV, HHV6, or ≥2 viremias were associated with more readmissions and longer LOS. One year OS rate was 78%. EOD by dsDNA viruses was associated with decreased 1-year OS. Infections by dsDNA viruses pose a substantial burden after TCD HCT. © 2017 The American Society for Blood and Marrow Transplantation
Keywords: t cell depletion; cytomegalovirus; cmv viremia; hhv6; adv viremia
Journal Title: Biology of Blood and Marrow Transplantation
Volume: 23
Issue: 10
ISSN: 1083-8791
Publisher: Elsevier Inc.  
Date Published: 2017-10-01
Start Page: 1759
End Page: 1766
Language: English
DOI: 10.1016/j.bbmt.2017.06.008
PROVIDER: scopus
PMCID: PMC5633047
PUBMED: 28668490
Notes: Article -- Export Date: 1 December 2017 -- Source: Scopus
Citation Impact
MSK Authors
  1. Yeon Joo Lee
    31 Lee
  2. Sergio Andres Giralt
    617 Giralt
  3. Miguel-Angel Perales
    461 Perales
  4. Molly Anna Maloy
    172 Maloy
  5. Yao-Ting Huang
    28 Huang
  6. Seong Jin   Kim
    12 Kim
  7. Daniel A Burack
    6 Burack